Abstract 1422: Candesartan-induced Upregulation Of Transcriptional Regulator Yin Yang 1 Blocks Leukocyte-endothelial Interaction Under Physiological Flow.
Abstract 1422: Candesartan-induced Upregulation Of Transcriptional Regulator Yin Yang 1 Blocks Leukocyte-endothelial Interaction Under Physiological Flow.
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摘要 1422：坎地沙坦诱导的转录调节因子阴阳 1 的上调可阻断生理流下白细胞与内皮细胞的相互作用。
作者：
H. Ishii;Daisuke Mori;Mayuko Sato;M. Yoshida
[目的]炎症相关基因的转录调控在动脉粥样硬化中起重要作用。我们已经报道了Yin Yang 1（YY 1）（一种转录调节因子）在血管平滑肌细胞增殖中的主导作用（圣地亚哥FS，石井H，et al. Circ Res in press）。然而，其在血管内皮中的作用仍不清楚。最近的观察指出血管紧张素II的一种新的“基因组”效应影响炎症。在这项研究中，我们研究了YY 1在血管紧张素II型受体阻滞剂（ARB）介导的白细胞-内皮细胞粘附调节流动条件下的潜在贡献。[方法和结果]将人脐静脉内皮细胞（HUVEC）与TNFα（5 ng/ml）共孵育4 h，加入或不加入坎地沙坦（1 μ M）。坎地沙坦可显著抑制TNFα激活的HUVEC与THP-1细胞的粘附（p <0.05）。[结论]坎地沙坦通过抑制VCAM-1的表达，上调了HUVEC中YY 1的表达，抑制了白细胞与内皮细胞的粘附。我们的研究结果表明，ARB通过YY 1依赖性机制发挥新的抗炎作用。
[Objective] Transcriptional control of inflammation-relevant genes plays an important role in atherosclerosis. We have reported a dominant role of Yin Yang 1 (YY1), a transcriptional regulator, in proliferation of vascular smooth muscle cells (Santiago FS, Ishii H, et al. Circ Res in press). However, its effect in vascular endothelium remains unclear. Recent observation points a novel “genomic” effect of Angiotensin II to influence inflammation. In this study, we examined a potential contribution of YY1 in angiotensin type II receptor blocker (ARB)-mediated modulation of leukocyte-endothelial adhesion under flow condition. [Methods and Results] Human umbilical vein endothelial cells (HUVEC) were co-incubated in the presence or absence of candesartan, an ARB (1 uM) for 4 hours with TNFα (5 ng/ml). Treatment with candesartan dramatically inhibited THP-1 cell adhesion to TNFα-activated HUVEC under static (p [Conclusion] We demonstrated that candesartan treatment upregulated YY1 in HUVEC and inhibited leukocyte-endothelial adhesion by inhibition of VCAM-1 expression. Our findings suggest a novel anti-inflammatory effect of ARB via YY1-dependent mechanisms.